Certain naturally occurring esters of cyclopropane carboxylic acids have long been known to possess insecticidal properties, but these compounds have been too easily degraded by ultra violet light to be of much use in agriculture. Several groups of synthetic compounds based on cyclopropane carboxylic acids (for example those disclosed in British Patent Specifications Nos. 1,243,858 and 1,413,491) have been evaluated in an attempt to discover compounds of sufficient light stability for use as general agricultural insecticides.
A particularly useful group of such compounds is that disclosed in British Patent Specification No. 2,000,764 and Belgian patent No. 863,151. These compounds combine good light stability with excellent contact and residual insecticidal properties, but, in common with the compounds described in British Patent Specification Nos. 1,243,858 and 1,413,491, they possess little or no fumigant activity. A further group of compounds, halobenzyl esters of 3-(2,2-dihalovinyl)-2,2-dimethylcyclopropane carboxylic acids, is described in Belgian patent No. 862,109 as having insecticidal properties but there is no indication that the compounds possess fumigant activity.
The present invention relates to certain novel benzyl esters of 3-(2,2-dihalovinyl)-2,2-dimethylcyclo propane carboxylic acids and 3-(2-halo(or trifluoromethyl)-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropane carboxylic acids with an extremely high level of insecticidal and acaricidal activity which may be used not only as contact or residual insecticides but also as fumigant insecticides.
Accordingly, this invention provides compounds of formula: ##STR1## wherein R.sup.1 and R.sup.2 are each selected from methyl, halomethyl, and halo; X is oxygen, sulphur, sulphonyl or a group NR.sup.4 where R.sup.4 represents hydrogen, lower alkyl or lower carboxylic acyl; R.sup.3 is lower alkyl, lower alkenyl or benzyl; m has the value zero or one, and n has a value from one to four.
The term "lower" is used herein in relation to "alkyl", "alkenyl" and "carboxylic acyl" groups to indicate such groups containing up to six carbon atoms, although such groups containing up to four carbon atoms are generally preferred.
In a preferred aspect the invention provides compounds of formula: ##STR2## wherein R.sup.1 and R.sup.2 are both chloro, or one of R.sup.1 and R.sup.2 is chloro and the other is trifluoromethyl, and R is methyl, ethyl, allyl, methoxy, ethoxy, allyloxy, ethylthio, ethylsulphonyl, dimethylamino, ethylamino, acetamido or N-methylacetamido. R is preferably in the 2- or 4-position with respect to the cyclopropane ester group.
Particular compounds according to the invention as defined by formula IA above include those set out in Table I herein in which the meanings for R.sup.1, R.sup.2 and R are given for each compound.
TABLE I ______________________________________ Compound No. R.sup.1 R.sup.2 R ______________________________________ 1 CF.sub.3 Cl 4-CH.sub.3 2 CF.sub.3 Cl 4-SC.sub.2 H.sub.5 3 Cl Cl 4-CH.sub.3 4 CF.sub.3 Cl 4-SO.sub.2 C.sub.2 H.sub.5 5 CF.sub.3 Cl 4-OCH.sub.3 6 CF.sub.3 Cl 2-CH.sub.3 7 CF.sub.3 Cl 4-OC.sub.2 H.sub.5 8 Cl Cl 4-OC.sub.2 H.sub.5 9 Cl Cl 4-C.sub.2 H.sub.5 10 CF.sub.3 Cl 4-C.sub.2 H.sub.5 11 Cl Cl 4-OCH.sub.3 12 Cl Cl 4-CH.sub.2 CH.dbd.CH.sub.2 13 CF.sub.3 Cl 4-CH.sub.2 CH.dbd.CH.sub.2 14 Cl Cl 4-OCH.sub.2 CH.dbd.CH.sub.2 15 CF.sub.3 Cl 4-n-C.sub.4 H.sub.9 16 CF.sub.3 Cl 4-OCH.sub.2 CH.dbd.CH.sub.2 17 CF.sub.3 Cl 3-CH.sub.3 18 Cl Cl 3-CH.sub.3 19 CF.sub.3 Cl 4-n-C.sub.3 H.sub.7 20 CF.sub.3 Cl 4-CH.sub.2 CH.dbd.C(CH.sub.3).sub.2 21 CF.sub.3 Cl 4-CH.sub.2 CH.dbd.CHCH.sub.3 22 CF.sub.3 Cl 4-CH.sub.2 C.sub.6 H.sub.5 23 CF.sub.3 F 4-NHCOCH.sub.3 24 CF.sub.3 F 4-N(CH.sub. 3)COCH.sub.3 25 CF.sub.3 F 4-N(C.sub.2 H.sub.5).sub.3 26 Br Br 4-OCH.sub.3 27 CH.sub.3 CH.sub.3 4-OCH.sub.3 28 CH.sub.3 CH.sub.3 4-CH.sub.2 CH.dbd.CH.sub.2 ______________________________________
Further compounds according to the invention include those of formula I above in which n is an integer of less than 4. Examples of such compounds are set out in Table II below.
TABLE II ______________________________________ No.Compound R.sup.1 R.sup.2 ##STR3## ______________________________________ 29 CF.sub.3 Cl ##STR4## 30 CF.sub.3 Cl ##STR5## ______________________________________
It will be appreciated by those skilled in the art that the compounds represented by formula I are capable of existing in various geometrical and stereoisomeric forms. Thus there may be cis and trans isomers arising from the substitution pattern of the cyclopropane ring, and E- and Z-isomers arising from the substituted vinyl group when R.sup.1 is not identical with R.sup.2. In addition two of the three carbon atoms of the cyclopropane are capable of existing in either R- or S-configurations since they are asymmetrically substituted.
Within the group of compounds represented by Formula I the cis isomers usually have better insecticidal properties than the trans isomers or the mixture of cis and trans isomers; the (+)-cis isomers being particularly preferred.
A particularly useful single isomer of a compound according to the invention is the 4-methyltetrafluorobenzyl ester of (+)-cis-3-(Z-2-chloro-3,3,3-trichloroprop-1-en-yl)-2,2-dimethylcyclopropan e carboxylic acid, which is believed to have the (1R,3R) configuration in the cyclopropane ring.
The compounds of the invention according to Formula I are esters and may be prepared by conventional esterification processes, of which the following are examples.
(a) An acid of formula: ##STR6## where Q represents the hydroxy group and R.sup.1 and R.sup.2 have any of the meanings given hereinabove, may be reacted directly with an alcohol of formula: ##STR7## where X, R.sup.3,n and m have any of the meanings given hereinabove, the reaction preferably taking place in the presence of an acid catalyst, for example, dry hydrogen chloride.
(b) An acid halide of formula II where Q represents a halogen atom, preferably a chlorine atom, and R.sup.1 and R.sup.2 have any of the meanings given hereinabove, may be reacted with an alcohol of formula III, the reaction preferably taking place in the presence or a base, for example, pyridine, alkali metal hydroxide or carbonate, or alkali metal alkoxide.
(c) An acid of formula II where Q represents the hydroxy group or, preferably, an alkali metal salt thereof, may be reacted with halide of formula: ##STR8## where Q.sup.1 represents a halogen atom, preferably the chlorine atom, X, R.sup.3, m and n have any of the meanings given hereinabove, or with the quaternary ammonium salts derived from such halides with tertiary amines, for example pyridine, or trialkyl amines such as triethylamine.
(d) A lower alkyl ester of formula (II) where Q represents a lower alkoxy group containing up to six carbon atoms, preferably the methoxy or ethoxy group, and R.sup.1 and R.sup.2 have any of the meanings given hereinabove, is heated with an alcohol of the formula III to effect a transesterification reaction. Preferably the process is performed in the presence of a suitable catalyst, for example, an alkali metal alkoxide, such as sodium methoxide, or an alkylated titanium derivative, such as tetramethyl titanate. PA0 Product A PA0 Product B PA0 Product C PA0 Product D PA0 Product E PA0 Product F PA0 Product G PA0 Product H PA0 Product J PA0 Product K PA0 Product L PA0 Product M PA0 Product N PA0 Product O PA0 Product P PA0 Product Q PA0 Product R PA0 Product S PA0 Product T PA0 Product U PA0 Product V PA0 Product W PA0 Product X PA0 Product Y PA0 Product Z PA0 Aphis fabae (aphids) PA0 Megoura viceae (aphids) PA0 Aedes aegypti (mosquitoes) PA0 Dysdercus fasciatus (capsids) PA0 Musca domestica (houseflies) PA0 Pieris brassicae (white butterfly, larvae) PA0 Plutella maculipennis (diamond back month, larvae) PA0 Phaedon cochleariae (mustard beetle) PA0 Telarius cinnabarinus (carmine spider mite) PA0 Aonidiella spp. (scale insects) PA0 Trialeuroides spp. (white flies) PA0 Blattella germanica (cockroaches) PA0 Spodoptera littoralis (cotton leaf worm) PA0 Chortiocetes terminifera (locusts) PA0 Diabrotica spp. (rootworms) PA0 Agrotis spp. (cutworms)
All of these conventional processes for the preparation of esters may be carried out using solvents and diluents for the various reactants where appropriate, and may be accelerated or lead to higher yields of product when performed at elevated temperatures or in the presence of appropriate catalysts, for example phase-transfer catalysts.
The preparation of individual isomers may be carried out in the same manner but commencing from the corresponding individual isomers of compounds of formula II. These may be obtained by conventional isomer separation techniques from mixtures of isomers. Thus cis and trans isomers may be separated by fractional crystallisation of the carboxylic acids or salts thereof, whilst the various optically active species may be obtained by fractional crystallisation of salts of the acids with optically active amines, followed by regeneration of the optically pure acid.
The optically pure isomeric form of the acid (or its equivalent acid chloride or ester) may then be reacted with the appropriate alcohol to produce a compound of formula I in the form of an individually pure isomer thereof.
The preparation of the compounds of formula II wherein Q is hydroxy, alkoxy or halo, and R.sup.1 and R.sup.2 are as defined hereinabove, useful as intermediates in the preparation of the compounds of the invention, is fully described in British Patent Specification No. 2,000,764 and in Belgian patent No. 863151, or British Patent Specification No. 1,413,491.
The compounds of formulae III and IV are believed not to have been described before. In a further aspect therefore the invention provides compounds of formulae III and IV wherein X, R.sup.3, m and n have any of the meanings given for the corresponding compounds of formula I, and where Q.sup.1 (in formula IV) is chloro or bromo. Preferred compounds of formulae III and IV are those corresponding to the compounds set out in Table I.
The compounds of formula III may be prepared by different processes depending upon the nature of the substituents in the benzene ring. Thus for alkyl- or alkenyl-substituted compounds of formula III where R.sup.3 is alkyl and m is zero the appropriately substituted alkyl- or alkenyl-fluorobenzene may be carboxylated (for example by the use of an organometallic reagent such as alkyl lithium, followed by decomposition of the reaction product with carbon dioxide) and subsequent reduction to the alcohol, using an appropriate reducing reagent, for example, lithium aluminium hydride.
The alkyl- or alkenyl-substituted fluorobenzenes used as starting materials in this sequence may be prepared by the alkylation of the appropriate fluorobenzenes using organometallic reagents such as alkyl lithium, and decomposing the reaction products with alkyl or alkenyl halides.
Alternatively the fluorobenzenes may be carboxylated first, and the resultant fluorobenzoic acids reduced to the benzyl alcohol which is then alkylated or alkenylated at a protected form (for example as the tetrahydropyranyl ether) using alkyllithium followed by reaction with an alkyl or alkenyl halide.
All of these processes are illustrated in the following scheme. ##STR9##
The compounds of formula III wherein X is sulphur or oxygen, may be prepared by displacement of halogen, e.g. fluorine, from an appropriately substituted fluorobenzyl alcohol, or the tetrahydropyranyl ether thereof. The following scheme illustrates the reactions used to prepare a number of compounds of formula III. ##STR10##
Similarly the compounds of formula III where X represents a group of formula NR.sup.4 (where R.sup.4 is as defined hereinbefore) may also be obtained from the corresponding fluorobenzyl alcohol. The following scheme illustrates the reactions involved in preparing some of these compounds. ##STR11##
Compounds of formula IV may be prepared by contacting a compound of formula ##STR12## with a source of positive halogen, such as an N-chloro- or N-bromoimide, for example, N-chlorosuccinimide and N-bromosuccinimide.
When the processes for preparing the compounds of Formula I are performed using intermediates which are themselves mixtures of isomers the products obtained will also be mixtures of isomers. Thus, the product would be a mixture of (.+-.)-cis and (.+-.)-trans isomers (perhaps with one form predominating) if the intermediate acid or acid derivative was used in the form of a mixture of (.+-.)-cis and (.+-.)-trans isomers. If a single isomer, of the acid, e.g. the (.+-.)-cis isomer with Z-configuration in the 2-chloro-3,3,3-trifluoropropenyl group, was used, the product would also be the single isomer of that stereochemical configuration, or a pair of isomers if there is an asymmetric carbon atom in the alcohol moiety.
In order to avoid confusion the products obtained by the processes described in the Examples herein are referred to as Products A to Z, each product being defined in terms of isomeric composition with reference to the compounds of Tables I and III as follows:
4-methyltetrafluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 1, Table I) consisting of 50% w/w of the (.+-.)-cis isomer and 50% w/w of the (.+-.)-trans isomer PA1 4-ethylthiotetrafluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 2, Table I) consisting of 50% w/w of the (.+-.)-cis isomer and 50% w/w of the (.+-.)-trans isomer PA1 4-methyltetrafluorobenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate (compound No. 3, Table I) consisting of 50% w/w of the (.+-.)-cis isomer and 50% w/w of the (.+-.)-trans isomer PA1 4-ethanesulphonyltetrafluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 4, Table I) consisting of 50% w/w of the (.+-.)-cis isomer and 50% w/w of the (.+-.)-trans isomer PA1 4-methoxytetrafluorobenzyl 3-(2-chloro-3,3,3-trifluoroproprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 5, Table I) consisting of 50% w/w of the (.+-.)-cis isomer and 50% w/w of the (.+-.)-trans isomer. PA1 2-methyltetrafluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 6, Table I) consisting of 50% w/w of the (.+-.)-cis isomer and 50% w/w of the (.+-.)-trans isomer. PA1 4-ethoxytetrafluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 7, Table I) consisting of 50% w/w of the (.+-.)-cis isomer and 50% w/w of the (.+-.)-trans isomer. PA1 4-ethoxytetrafluorobenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate (compound no. 8, Table I) consisting of 50% w/w of the (.+-.)-cis isomer and 50% w/w of the (.+-.)-trans isomer. PA1 4-methyltetrafluorobenzyl (.+-.)-cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate (compound no. 3, Table I) in its (.+-.)-cis isomeric form. PA1 4-methyltetrafluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 1, Table I) in its (.+-.)-cis isomeric form. PA1 4-ethyltetrafluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 10, Table I) in its (.+-.)-cis isomeric form. PA1 4-methoxytetrafluorobenzyl 3-(2,2-dichlorovinyl)2,2-dimethylcyclopropane carboxylate (compound no. 11, Table I) in its (.+-.)-cis isomeric form. PA1 4-n-butyltetrafluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 15, Table I) in its (.+-.)-cis isomeric form. PA1 4-alkoxytetrafluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 16, Table I) in its (.+-.)-cis isomeric form. PA1 4-methoxytetrafluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 5, Table I) in its (.+-.)-cis isomeric form. PA1 3-methyltetrafluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 17, Table I) in its (.+-.)-cis isomeric form. PA1 3-methyltetrafluorobenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate (compound no. 18, Table I) consisting of 50% w/w of the (.+-.)-cis isomer and 50% w/w of the (.+-.)-trans isomer. PA1 4-allyltetrafluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 13, Table I) in its (.+-.) cis isomeric form. PA1 4-n-propyltetrafluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 19, Table I) in its (.+-.)-cis isomeric form. PA1 4-allyltetrafluorobenzyl 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate (compound no. 12, Table I) consisting of 50% w/w of the (.+-.)-cis isomer and 50% w/w of the (.+-.)-trans isomer. PA1 4-(3-methylbut-2-en-1-yl)tetrafluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 20, Table I) in its (.+-.)-cis isomeric form. PA1 4-(but-2-en-1-yl)tetrafluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 21, Table I) in the form of a mixture of 50% of the E-butenyl and 50% of the Z-butenyl isomeric forms of the (.+-.)-cis isomeric form (with respect the cyclopropane ring). PA1 4-allyl-2,6-difluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 30, Table II) in its (.+-.)-cis isomeric form. PA1 4-allyl-3,5-difluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 29, Table II) in its (.+-.)-cis isomeric form. PA1 4-benzyltetrafluorobenzyl 3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropane carboxylate (compound no. 22, Table I) in its (.+-.)-cis isomeric form.
The compounds of formula I may be used to combat and control infestations of insect pests and also other invertebrate pests, for example, acarine pests. The insect and acarine pests which may be combatted and controlled by the use of the invention compounds include those pests associated with agriculture (which term includes the growing of crops for food and fibre products, horticulture and animal husbandry), forestry, the storage of products of vegetable origin, such as fruit, grain and timber, and also those pests associated with the transmission of diseases of man and animals.
In order to apply the compounds to the locus of the pests they are usually formulated into compositions which include in addition to the insecticidally active ingredient or ingredients of formula I suitable inert diluent or carrier materials, and/or surface active agents. The compositions may also comprise another pesticidal material, for example another insecticide or acaricide, or a fungicide, or may also comprise a insecticide synergist, such as for example dodecyl imidazole, safroxan, or piperonyl butoxide.
The compositions may be in the form of dusting powders wherein the active ingredient is mixed with a solid diluent or carrier, for example kaolin, bentonite, kieselguhr, or talc, or they may be in the form of granules, wherein the active ingredient is absorbed in a porous granular material for example pumice.
Alternatively the compositions may be in the form of liquid preparations to be used as dips or sprays, which are generally aqueous dispersions or emulsions of the active ingredient in the presence of one or more known wetting agents, dispersing agents or emulsifying agents (surface active agents).
Wetting agents, dispersing agents and emulsifying agents may be of the cationic, anionic or non-ionic type. Suitable agents of the cationic type include, for example, quaternary ammonium compounds, for example cetyltrimethyl ammonium bromide. Suitable agents of the anionic type include, for example, soaps, salts of aliphatic monoesters or sulphuric acid, for example sodium lauryl sulphate, salts of sulphonated aromatic compounds, for example sodium dodecylbenzenesulphonate, sodium, calcium or ammonium lignosulphonate, butylnaphthalene sulphonate, and a mixture of the sodium salts of diisopropyl- and triisopropyl-naphthalene sulphonates. Suitable agents of the non-ionic type include, for example, the condensation products of ethylene oxide with fatty alcohols such as oleyl alcohol or cetyl alcohol, or with alkyl phenols such as octyl phenol, nonyl phenol and octyl cresol. Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, the condensation products of the said partial esters with ethylene oxide, and the lecithins.
The compositions may be prepared by dissolving the active ingredient in a suitable solvent, for example, a ketonic solvent such as diacetone alcohol, or an aromatic solvent such as trimethylbenzene and adding the mixture so obtained to water which may contain one or more known wetting, dispersing or emulsifying agents.
Other suitable organic solvents are dimethyl formamide, ethylene dichloride, isopropyl alcohol, propylene glycol and other glycols, diacetone alcohol, toluene, kerosene, white oil, methylnapthalene, xylenes and trichloroethylene, N-methyl-2-pyrrolidone and tetrahydro furfuryl alcohol (THFA).
The compositions to be used as sprays may also be in the form of aerosols wherein the formulation is held in a container under pressure in the presence of a propellant such as fluorotrichloromethane or dichlorodifluoromethane.
The compositions which are to be used in the form of aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient or ingredients, the said concentrate to be diluted with water before use. These concentrates are often required to withstand storage for prolonged periods and after such storage, to be capable of dilution with water to form aqueous preparations which remain homogenous for a sufficient time to enable them to be applied by conventional spray equipment. The concentrates may contain 10-85% by weight of the active ingredient or ingredients. When diluted to form aqueous preparations such preparations may contain varying amounts of the active ingredient depending upon the purpose for which they are to be used. For agricultural or horticultural purposes, an aqueous preparation containing between 0.0001% and 0.1% by weight of the active ingredient is particularly useful.
In use the compositions are applied to the pests, to the locus of the pests, to the habitat of the pests, or to growing plants liable to infestation by the pests, by any of the known means of applying pesticidal compositions, for example, by dusting or spraying.
The compositions of the invention are very toxic to wide varieties of insect and other invertebrate pests, including, for example, the following:
The compounds of formula I and compositions comprising them have shown themselves to be particularly useful in controlling lepidopteran pests of cotton, for example Spodoptera spp. and Heliothis spp. The fumigant properties of the compounds enable them to be used to combat pests which inhabit the soil, for example Diabrotica spp. They are also excellent knock down agents and as such may be used in conjunction with other insecticides to combat public health pests such as flies. They are also very useful in combatting insect and acarine pests which infest domestic animals, such as Lucilia sericata, and ixodid ticks such as Boophilus spp., Ixodes spp., Amblyomma spp., Rhipicephalus spp., and Dermaceutor spp. They are effective in combatting both susceptible and resistant strains of these pests in their adult, larval and intermediate stages of growth, and may be applied to the infested host animal by topical, oral or parenteral administration.